Irv Arons' Journal

This journal will be a spot for me to comment about the world of ophthalmics and medical lasers. I intend to publish some of the more than 150 articles and columns that I have written on these subjects.
In addition, I will report on the latest information on new drugs and devices for the treatment of retinal diseases, including age-related macular degeneration (AMD).

Wednesday, May 31, 2017

A Most Memorable Trip: The Soviet Union Before the Breakup - The Interesting Adventures of A Consultant

Irv Arons

In the summer of 1990, my wife and I were invited to
join a People to People Ambassador Tour to visit the Soviet Union. The
USSR didn’t break up into its member states until the following year,
late 1991. So, we got a look at what turned out to be a huge national
facade – a strong military front and a “third world” infrastructure.

I
was part of a medical group (medical laser specialists) that visited
several hospitals and laser centers (?) within Moscow (Russia), Tbilisi (Soviet
Georgia), Kharkov (Ukraine) and in St. Petersburg (again, in Russia). Fortunately, my wife
was able to join up with a group of performing artists that were also on
an Ambassador tour and, while we (the medical group) were doing our hospital visits, they
visited their Soviet peers,.

For the record, Moscow was bleak,
with the exception of our visit to the Kremlin, and the gift shopping –
my wife got a beautiful amber necklace from a street vendor for $20, and
I came back with a set of matryoshka (nesting) dolls, with Gorbachev on
top and Lenin deep inside at the bottom). In contrast, Tbilisi in Soviet Georgia
was colorful and hot (90 degrees when we were there). The Ukraine, our
next stop, was the food basket of Russia, but because they had few
refrigerated trucks, there was no way of moving the food into the
cities! Our final stop was St. Petersburg (or Leningrad, whichever you
prefer), which was beautiful. It is a land of rivers and bridges – and
the Hermitage, the most beautiful museum that we have ever visited!

A
brief anecdote – the day before our visit to the Hermitage, one of my
colleagues ran out of 35 mm film and I gave him a couple of rolls of the
400 speed film that I was using. The next day, he replaced my rolls
with a couple of rolls of 1000 speed film, which enabled me to take some
beautiful pictures inside the Hermitage, including of the huge
malachite urns and a couple of Rembrandt paintings (one of a man in a
red coat - which I believe was a self-portrait, and Moses with his son
Isaac on the mount) without needing to use a flash, which was forbidden
inside the museum. I have included
a few of these photos for your enjoyment – actually, the Rembrandt’s are from
the web, as they are much better reproductions than I was able to
achieve from my 35mm slides.)

We flew Aeroflot within the
USSR – no seat belts, animals on board, and tea service served in
cracked cups by heavy-set women with gold teeth! The planes were flown
by military pilots, who were the first to get off, and the rear section
of the plane was unloaded first to keep the planes balanced!

When we visited,
most people worked for the state – and there wasn’t any work! So they
would go to their jobs in the morning and, having nothing to do there,
would be back on the streets by noon. It just goes to prove that the
communist way of doing things didn’t work. There were no goods in the
stores, and what we did see was both sparse and of poor quality (paper
shoes?). And, long lines everywhere to get tobacco and vodka.

Based
on my experiences, I published two articles about my trip; one about
the state of healthcare (and lack of lasers) in the USSR, and a second
on the state of eyecare in that part of the world. They are technical in
nature but illustrate the differences between what the Soviet Union was
telling the world and what we actually saw!

Here, for your further enlightenment, are the two articles I wrote about our (the medical groups’) experiences.

During
late July 1990, I was privileged to join a delegation of medical laser
specialists and other health care professionals, under the auspices of
the People to People Ambassador Program, invited to tour the medical
community in the Soviet Union. Our group, organized by the American
Society for Lasers in Medicine and Surgery, was composed of specialists
in gynecology, plastic surgery, thoracic surgery, urology, general
medicine, and myself, representing the field of ophthalmology. In
addition to the ASLMS group, a veterinarian working with lasers, a
health care safety specialist, and two medical technical/clinical lab
specialists were included in our delegation.

We were able to
visit a medical laser research institute in Moscow, and four hospitals,
one each in Moscow (Soviet Russia), Tbilisi (Soviet Georgia), Kharkov
(Soviet Ukraine), and Leningrad/St. Petersburg (Soviet Russia, again).

Our
overall impression was that the facilities and equipment in use were
woefully decrepit and/or non-existent or years behind Western standards.
However, the medical personnel we met were dedicated professionals.

Of
particular note, we found that the hospitals -- even one claimed to be
only three years old -- were ill kept and falling apart. The facades
were cracked and broken, the hallways and stairwells unswept, and the
grounds surrounding the buildings not cared for at all. In counterpoint,
we found the patient rooms were clean and staffed with dedicated nurses
and doctors doing their best with what they had. This was particularly
evident at the Karzigan Childrens Hospital in Moscow. The wards were
filled with children with trauma of all kinds, but they were all smiling
and very well cared for by an attentive staff of nurses and aides. It
was here that we learned that a typical doctor with less than 10 years
service earns between 240-260 rubles a month (the equivalent to about
$40 at the official exchange rate of 6 rubles to the dollar, and only
$20-30 at the black market exchange rate of 10-15 rubles to the dollar),
a beginning research worker earns 140-150 rubles per month, and a
surgical nurse get about 110 rubles for regular shifts. (In contrast,
the bus drivers providing our transportation were paid 400 rubles/month
and we were told that street sweepers earned as much as 700
rubles/month!)

The hospital equipment, especially for diagnosis
and surgery, was particularly non-existent, and, according to our
laboratory clinicians, the clinical laboratory equipment was barely
adequate to care for the patients in the wards. But we must emphasize,
both the hospital administration and medical staff were dedicated to
providing the best care possible to their patients. What they lacked in
equipment they more than made up with in numbers and dedication.

As
for medical lasers, and new medical treatments using lasers, except for
the laser institute in Moscow, the only lasers that the hospitals
seemed to have were low powered therapeutic types, basically HeNes and
GaAs infrared lasers. The hospital in Leningrad had several CO2 lasers,
and claimed to have other surgical equipment, but we only saw
therapeutic lasers in operation. We were told that only about 100 of
approximately 15,000 hospital-based physicians in Kharkov have access to
or use surgical lasers. We would guess that the percentages are not
much different in the other 14 Soviet Republics. At the hospitals we
visited, the majority of the half dozen lasers they claimed to have --
if they had any -- were either HeNe or GaAs therapy lasers, used to
treat open sores, pain, and in one hospital in Tbilisi (Soviet Institute
of Clinical & Therapeutical Research), for treating myocardial
infarctions by clearing viruses in the blood through intravenous use of a
HeNe laser connected to a fiber inserted through an arm vein. The same
hospital also used a scanning HeNe laser to alleviate angina chest pain
by scanning the laser beam across the patient's chest!

At a
trauma hospital in Leningrad (The Ambulatory Institute Hospital), we saw
a 40-50 watt CO2 laser in the corner of an operating room, and another
upstairs in a storeroom along with the usual HeNe lasers. We saw no
evidence of a YAG laser although the laser specialist at this hospital
claimed to have just received one, but which he had not yet unpacked. In
the same storeroom with the spare CO2 laser, we were told that a small
laser sitting on top of packing crates was a new UV laser, apparently
solid-state since there was no evidence of any gas bottles or
connections for one. (An interesting side note, we observed a burn
therapy ward at this hospital, and it was disconcerting to see flypaper
strips hanging from the ceiling.)

At the hospital in Kharkov (The
Central Regional Hospital), we were told that they had an Ar laser used
in ophthalmic treatments (but we did not see it).

The National
Research Institute of Laser Surgery in Moscow claimed to be doing
considerable research with medical lasers, performing 47,000 laser
procedures annually. It is supposedly, one of 52 laser centers in the
Soviet Union. We were given a presentation about the clinical research
they were doing with five types of high power lasers, mostly CO2 and YAG
-- and two prototype free electron lasers, used for PDT studies. The
FELs, according to the slides shown us, may be revolutionary, in that
they appeared to be about the size of a large sized desk, much smaller
than any other FEL I have seen -- and I have seen the Stanford FEL and
pictures of others. Attempts to find out more about this laser
development were fruitless, however I plan to get back in touch with my
contact at the Institute to see if I can possibly learn more about this
exciting laser development. (Several weeks after my return to the
States, I received a call telling me that a defector from the Moscow
Laser Institute wanted me to know that he had built the laser in
question and it was not an FEL, but rather an electron beam generator
pumping a chemical laser use in their PDT work.) When we asked to see
their lasers, we were politely told that they were in another building
and couldn't be shown to us. Apparently, the person holding the key to
the lab was not available!

According to a profile of the Soviet
healthcare community recently published by Medistat, a UK healthcare
publication, what we saw in the Soviet Union this summer is typical and
not out of line with what others have reported. The Medistat profile
stated that the Soviet Union has some 23,000 hospitals with 3.6 million
beds, and in addition, some 38,000 polyclinics and other outpatient
centers. Capital investment in recent years has concentrated on the
construction of new facilities to boost the number of beds, but many of
the new facilities have been built at unsuitable sites, and the majority
of Soviet hospitals having little in modern equipment with some lacking
the basic necessities of adequate sanitary facilities or even heating.

The
polyclinic is the main unit in the primary healthcare network, and the
first point of contact for most Soviet patients. They serve districts of
50,000 to 60,000 inhabitants and are staffed by doctors responsible for
around 2000 patients. In addition to general doctors, each polyclinic
has specialists in area such as cardiovascular disease, oncology and
renal medicine.

The Soviet Union has the highest number of
doctors per capita, with a total of 1.3 million doctors serving a
population of 275 million. In addition, there are 3.3 million medical
assistants. Women doctors are well represented, accounting for about 70%
of all doctors. (We were told the percentage was closer to 50%, at
least at the facilities we visited.)

As you know, until recently,
all planning was done centrally, and for five years in advance -- the
so called Five Year Plan. The most recent healthcare plan was put
together in August 1987. That five-year plan attempted to address the
chronic underfunding of the healthcare system, calling for new hospitals
while neglecting older ones which will now need to undergo drastic
major refurbishment. Expenditures for medical equipment had also been
limited in the past, with the majority of funds allocated for new
buildings. But the new policy included allocation of more resources for
the purchase of modern equipment, in particular the polyclinic
facilities were to be upgraded with proper diagnostic and treatment
services to enable the patients to be treated at the clinic rather than
to be referred to local hospitals. According to Medistat, 5.4 million
rubles had been allocated for the purchase of new equipment over the two
year period 1988-1989.

Discussing the state of the Soviet
medical equipment market, Medistat states that the USSR suffers from a
chronic shortage of equipment, particularly in the high tech areas such
as computerized scanning, ultra-sound, renal equipment, and as we found
out, laser treatment devices. Even basic equipment such as
electrocardiographs and routine surgical instruments and disposable
syringes are in short supply, with the problem being further aggravated
by the fact that much of the Soviet produced equipment is sub-standard.

The
current five-year plan envisages accelerating development in the
medical industry and raising the technological level both within its
industry and in its healthcare facilities. We hope that this can be
accomplished. It is sorely needed.

In the report above, I
discussed the state of healthcare in the USSR as we saw it in 1990. The
hospitals and care appeared to be at least thirty years behind similar
Western facilities, with a lack of instruments and supplies and
crumbling buildings, but with dedicated medical personnel.

At the
urging of a friend, I have added a brief piece, taken from Wikipedia,
about how the healthcare system in the Soviet Union (and more
specifically Russia) has changed since I was there – and from the way it
is described below, it really hasn’t!

Pre-1990s
Soviet Russia had a totally socialist model of health care with a
centralised, integrated, hierarchically organised with the government
providing free health care to all citizens. All health personnel were
state employees. Control of communicable diseases had priority over
non-communicable ones. On the whole, the Soviet system tended to primary
care, and placed much emphasis on specialist and hospital care.

The
integrated model achieved considerable success in dealing with
infectious diseases such as tuberculosis, typhoid fever and typhus. The
effectiveness of the model declined with underinvestment. Despite the
fact that the quality of care began to decline by the early
1980s,medical care and health outcomes were on par with western
standards. Despite a doubling in the number of hospital beds and doctors
per capita between 1950 and 1980, the lack of money that had been going
into health was patently obvious. Some of the smaller hospitals had no
radiology services, and a few had inadequate heating or water. A 1989
survey found that 20% of Russian hospitals did not have piped hot water
and 3% did not even have piped cold water. 17% lacked adequate
sanitation facilities. Every seventh hospital and polyclinic needed
basic reconstruction. Five years after the reforms described below per
capita spending on health care was still a meagre US$158 per year (about
8 times less than the average European social models in Spain, the UK
and Finland, and 26 times that of the U.S. which spent US$4,187 at that
time).

Reform in 1991-1993

The new Russia has changed to a
mixed model of health care with private financing and provision running
alongside state financing and provision. Article 41 of the 1993
constitution confirmed a citizen's right to healthcare and medical
assistance free of charge. This is achieved through compulsory medical
insurance (OMS) rather than just tax funding. This and the introduction
of new free market providers was intended to promote both efficiency and
patient choice. A purchaser-provider split was also expected to help
facilitate the restructuring of care, as resources would migrate to
where there was greatest demand, reduce the excess capacity in the
hospital sector and stimulate the development of primary care. Finally,
it was intended that insurance contributions would supplement budget
revenues and thus help to maintain adequate levels of healthcare
funding.

The OECD reported that unfortunately, none of this has
worked out as planned and the reforms have in many respects made the
system worse. The population's health has deteriorated on virtually
every measure. Though this is by no means all due to the changes in
health care structures, the reforms have proven to be woefully indequate
at meeting the needs of the nation. Private health care delivery has
not managed to make much inroads and public provision of health care
still predominates.

The resulting system is overly complex and
very inefficient. It has little in common with the model envisaged by
the reformers. Although there are more than 300 private insurers and
numerous public ones in the market, real competition for patients is
rare leaving most patients with little or no effective choice of
insurer, and in many places, no choice of health care provider either.
The insurance companies have failed to develop as active, informed
purchasers of health care services. Most are passive intermediaries,
making money by simply channeling funds from regional OMS funds to
healthcare providers.

National Projects

In 2006 a national
project 'Health' was launched to improve the country's healthcare
system through improved funding and healthcare infrastructure. This plan
helped equip hospitals and clinics with advanced, high-end equipment
and ambulance systems, build new medical centers, as well as launch
nation-wide vaccination programs and free health checks. The project has
also been working on developing medical technology market through
initiatives to blend healthcare and information technology. One of the
focuses was made on salary increase of medical staff working in the
primary care as well as their wider training programs.

The
project was initiated by the Russian President Vladimir Putin and
coordinated by the Presidential administration. It was mostly financed
by the federal budget. However regional and municipal levels have also
contributed a lot to the financing of the program.

Reform in 2011

After
Vladimir Putin became president in 2000, there was significant growth
in spending for public healthcare and in 2006 it exceed the pre-1991
level in real terms. Also life expectancy increased from 1991-93 levels,
infant mortality rate dropped from 18.1 in 1995 to 8.4 in 2008. Russian
Prime Minister Vladimir Putin announced a large-scale health-care
reform in 2011 and pledged to allocate more than 300 billion rubles ($10
billion) in the next few years to improve health care in the country.
He also said that obligatory medical insurance tax paid by companies for
compulsory medical insurance will increase from current 3.1% to 5.1%
starting from 2011.[27] Russia, anyhow, maintains several centers of
excellence, such as the Fyodorov Eye Microsurgery Complex, founded in
1988 by Russian eye surgeon Svyatoslav Fyodorov. (See my next writeup,)

I
have just returned from a two week tour of four cities within the
Soviet Union. I had anticipated telling you about the state of eyecare
within the USSR, but unfortunately, our visit to the premier Moscow
Research Institute of Eye Microsurgery was canceled at the last minute,
as we were informed by Dr. Fyodorov that the "Institute will be closed
in July for preventative maintenance," and that "your visit at the term
(sic) you have stated is inexpedient." We had originally been invited
following my February letter requesting to have our delegation visit the
clinic. In fact, in late June we were told that we were welcome to
visit the clinic, which was scheduled to shut down in August for
holiday.

Apparently, the hotel we stayed at in Moscow, the
Kosmos, is part of the Intourist program to provide visitors with eye
care at Fyodorov's Moscow clinic. We found a brochure advertising
"Beautiful Eyes for Everybody," and describing how the Moscow Research
Institute of Eye Microsurgery "treats 22,000 people annually, restoring
or improving vision and removing the need to wear eyeglasses for many."
In addition to RK (radial keratotomy), the clinic claims to do laser
treatment of secondary cataract, laser treatment of glaucoma, and laser
treatment of "complicated myopia of high degree." (It must be one of
the only facilities with surgical lasers in the USSR, as we visited a
laser research institute and three hospitals and saw very few surgical
lasers -- mostly therapeutic HeNe and GaAs biostimulation type devices.)

The
brochure goes on to state that your pre-operative stay is arranged at
the Kosmos, and following the outpatient surgery, your post-operative
treatment is done at the hotel by a team of qualified doctors and
nurses. Foreign patients are offered a program of excursions, including
theater tickets (the ballet only costs 4 rubles -- the equivalent of 30
cents at the black market exchange rate) and other services offered by
Intourist. Fyodorov hopes to treat 20,000 foreigners a year by 1992.

A
recent profile of Fyodorov in Fortune (May 1989) talked about the
Fyodorov entrepreneurship, with his clinic being a $75 million a year
business, and growing at 30% a year annually. The clinics have over
5000 employers located at nine treatment centers across the Soviet
Union, and include two factories producing eyeglasses and surgical
instruments. (In addition, Dr. Fyodorov recently spent some $12 million
outfitting an 11,000 ton "floating eye hospital" called the Floks,
which travels from port to port in the Persian Gulf offering RK and
other eye surgeries.)

Having missed out on the opportunity to
visit with Dr. Fyodorov, I would like to offer some personal
observations about eye care in the Soviet Union. As previously
mentioned, our People-to-People delegation of medical laser specialists
visited Moscow (Soviet Russia), Tblisi (Soviet Georgia), Kharkov (Soviet
Ukraine), and Leningrad (back in Russia). We saw very few optical
shops (none that were open) and only a small number of Soviet citizens
wearing eyeglasses! One ophthalmologist at a central hospital in
Kharkov told me that 50% of the people need corrective lenses -- similar
to the percentages in the rest of the world -- but we saw very few
people wearing lenses. If 5% of the people in the streets had glasses,
that's a lot. This says that Western technology and entrepreneurship
could provide a needed service in the Soviet Union if a way could be
found to open (and stock) optical retail shops in the major cities.
However, you must remember that the average citizen only earns about 200
rubles per month (the equivalent of about $350/month at the "official"
business exchange rate or about $10-15/month at the black market
exchange rate of 10-15 rubles to the dollar). Therefore, the price of
eyewear would have to be low for the average person to be able to afford
it -- unless the health care system can be convinced to reimburse or
pay for the glasses. (The government health care system pays Fyodorov's
clinic the equivalent of $300 for each RK procedure carried out.)

If
a Moscow McDonalds can generate hours long lines for a $5 "Big Mac",
why not $20-40 eyeglasses at a Moscow Lenscrafters or a Leningrad Pearle
Vision Center?

A First Trip to Japan: The Interesting Adventures of A Consultant

Irv Arons

In the summer of 1979, I had been hired to conduct a survey of all of the major contact lens companies operating around the world, for a US company interested in finding a partner for its contact lens company. I had completed my interviews of the companies in the US and Europe, and now had to interview the two companies producing lenses in Japan. Since this was my first trip to Japan, I decided to combine business with pleasure and took my wife along to spend a week on vacation, visiting Tokyo and Kyoto, before I was to meet up with a colleague from the Arthur D. Little (ADL) Tokyo office, who would act as my interpreter and take me to my meetings in Osaka and Nagoya.

The first leg of the trip was a three-day contact lens conference being held in San Francisco. There, I met up with a friend who ran a contact lens practice in Hawaii. Since he had clients who were on the management staff of Japan Airlines (who would be flying us from San Francisco to Tokyo), he was kind enough to arrange for my wife and I to be upgraded to First Class for our flight to Tokyo. (That was our first experience flying internationally in First Class and we liked it so much that I decided to upgrade our return tickets – at a cost of $600 each, as I recall, to fly First Class on our return flight from Tokyo to Boston. An excellent decision, as it was about a twelve-hour flight.)

We arrived in Tokyo and managed to find our way via bus from Narita airport to Tokyo Central Station, and to get a taxi to take us to our hotel, the Okura, in central Tokyo and near the ADL Tokyo office.

Our first venture out of the hotel was to the downtown shopping district of Tokyo. We had learned from our travel guide books that the best place to eat was at the restaurants located within the major department stores, up on the fifth floor. What the guide books neglected to tell us was that very few people spoke English and since we spoke only a few words of Japanese, we were left with only hand gestures!

At least at the restaurant, there were pictures of the several dishes available, and by pointing to the ones we wanted, we had a reasonable chance of getting something we could eat. But the next dilemma, the meals were served in a stack of bowls, and of course, with chop sticks. Was the top bowl broth or soup, or to wash your hands? And, if it is soup how do you eat it without spoons? Finally, another customer, sitting at a nearby table, sensing our discomfort, took pity on us and gestured to hold the bowl to your mouth and sip from it. So, that problem was solved.

The next day, I wanted to walk to the ADL Tokyo office that I was told was close by, so that I would know where it was for the following week when I had to check in. The street signs were a complete mystery and I had no idea how to get from the hotel to the office, even though I had instructions and a map!

Two Japanese men, passing by, sensed my dilemma and offered to help. After showing them the address of the office, they were kind enough to walk us right to the building, a very generous offer from strangers. The second offer of kindness to strangers from the Japanese people.

We had planned on spending a few days exploring Tokyo and then take a trip via the bullet train to Kyoto, the Japanese shrine city. However, our plans got changed because of a chance meeting at a coffee shop that afternoon.

An older gentleman introduced himself to us, while we were enjoying our coffee (or tea, I don’t recall). It turned out that he was a retired military officer, and also a former member of parliament. He offered to act as our tour guide and show us the real Tokyo and then take us to see Mount Fuji.

Since our plans were flexible, we agreed to his offer and arranged to meet him the following morning at the coffee shop for a guided tour of Tokyo. We hired a taxi for the day and our new guide took us to see and walk through the Parliament building and showed us several historic sites around the city. We ended that day with a visit to the Kabuki theater, being taken in through the people’s entrance and were able to watch the show from the first balcony. Quite an experience.

We enjoyed the tour so much, we agreed to let him be our tour guide the following day and take us to visit Mount Fuji, taking the bullet train (as long as we paid his fare). However, the weather didn’t cooperate and when we got to the mountain, it was completely fogged in. On the way back to Tokyo, we had another interesting experience. Three young women were on the opposite seats from us on the train and attempted to engage us in conversation. They claimed to be English teachers (or maybe students studying to be teachers) and wanted to practice their English with us. To be honest, we could barely understand them.

Since that was our last day of sightseeing, our gentleman guide asked us to meet him at a local Chinese restaurant that evening for a farewell dinner and to meet a few of his friends from the Kabuki theater. Little did we know that he had arranged for us to get the bill at the end of the evening and I got hit with a $250 check! (Recall that this was 1979, and the exchange rate for the yen was quite in my favor, about 350 yen to the dollar, but this was still an expensive meal!) I guess that was his way of getting paid back for acting as our tour guide for the couple of days we spent with him.

The next day, I left my wife at the hotel and made my way to the ADL Tokyo office to begin the business part of my trip, to visit the two contact lens companies in Nagoya and Osaka. (No wives allowed on business trips in Japan!)

My First European Trip: The Interesting Adventures of A Consultant

Irv Arons

Recall that I had toured Europe in the fall of 1979, visiting the various contact lens companies that were based there, as well as interviewing notable doctors involved in their use, on an assignment to assess the contact lens companies in both the U.S. and Europe for a Japanese client interested in acquiring technology for starting a contact lens business in Japan.

This was my first trip to Europe and I kept a diary of my daily travels – the first and only time I have ever done so. It’s a good thing I did, because there were several interesting incidents that occurred that you might enjoy.

I flew from Boston to JFK, to pick up my flight to London. I arrived in London at 10 PM, and quickly realized a had made a big mistake. I had a fairly large piece of luggage (I would be gone for over a week.), and hadn’t taken my wheels! (This was the fall of 1979, before wheeled luggage was in general use.) I made it onto the subway and got into London from Heathrow and finally found my hotel, the Bristol. Except they didn’t have my reservation! Luckily they had one room left and I took it and went to sleep without supper, as the kitchen wasn’t open at that time of night.

The next morning, I met my ADL colleague from our London office, who would be my traveling companion (and translator). It turned out, the London office had made my hotel reservations at another hotel, and forgot to notify me. (Again, these were the days before email.) We then went on to the several meetings that we had arranged in the London area. I went to the final one that evening by myself – no problem – they speak Bloody English!

That evening my colleague had arranged for us to meet at a nearby pub for a dinner show. I was quite surprised to find that he and his girlfriend had brought along another girl, his girlfriend’s roommate, whose boyfriend was out of town. After the dinner and show, I got dropped off at my hotel (alone) because we had a busy next day – four interviews and then flying off to Paris.

After our interview in Paris, the next day, we flew on to Strasbourg and our drive to Freiberg for a contact lens conference. We drove through very beautiful farm land and took a local inland route to the Rhine river and across into Germany at a local crossing. The border guards stopped us, took our passports, and searched our luggage thoroughly. They were puzzled by my voltage converter (European to 110v for my electric shaver), but after about ten minutes, finally allowed us to proceed into Germany and we went on to Freiberg and the CL conference.

I spent the weekend on my own, as my colleague took the train to Frankfort to spend some time with friends, after buying me a ticket for my Sunday train ride. Since I speak no German (although understand a little based on my Jewish background), I somehow managed to survive the weekend since I knew the word for chicken (hundchen!).

When I got to the train station on Sunday morning, I couldn’t figure out which track the Frankfort train was on, but luckily, some English gentlemen saw my dilemma and helped me out. It turned out that they were the world famous Amadeus Quartet and also going to Frankfurt. I thoroughly enjoyed my train ride talking to them.

Arriving at the Frankfurt station, I met my ADL colleague and we took the train to our next stop, Aschaffenburg. We arrived early in the evening, and after dinner, went to a movie and I saw Moonraker in German and didn’t understand a word of it!

Following our nearly all day meeting in Aschaffenburg, we took a taxi to the Frankfurt airport for our flight back to London. After leaving my luggage to walk to the gate, I thought I heard my name over the loudspeaker, but since the announcement was in German, I wasn’t sure. Sure enough, when we arrived in London, I quickly discovered that my bag was still in Frankfort.

I didn’t panic too much, but since we were going out of London the following day for two days of meetings, I decided all I needed was a clean shirt and some deodorant to get me through until my bag showed up in London. I quickly went out to try and find a shirt and the only store open had a dress shirt that set me back 27 pounds (or about $50). Finally, about 8 PM that night I got a call that my luggage had made its way to London and would be delivered to my hotel room. You can be sure I got up early the next morning, before our trip out of town and returned that $50 shirt! (I kept the deodorant.)

After a few meetings in London, we took the train to Birmingham, had a couple of meetings there and on to Loughborough.

After several meetings, it was on to Hitchins and then Hempel Hempstead. (Yes, I did get to see quite a bit of England on that trip.)

The next day was my last in England and after several more meetings, I made my way via the subway to the airport and finally got on my flight back to the States.

After what I saw of the beauty of Europe, I made a promise that someday I would return. (And, my wife and I did. A few years later we took a sixteen day tour of eight countries - “If it was Tuesday, it must be Belgium!” As it turned out, we did travel through Belgium on our way from Paris to Amsterdam on a Tuesday.)

We have since gone back to Europe several times, particularly to Switzerland and to Spain, and even took a river boat trip down the great rivers of Europe, from Amsterdam to Vienna, passing through sixty-six locks along the way.

The Soft Contact Lens Industry and My Role in its Growth: The Interesting Adventures of A Consultant

Irv Arons

The Bausch & Lomb Soflens, the original soft contact lens, was first approved for marketing in March 1972, My first contact lens assignment began in June of that year, an assessment of the “safety and efficacy” of the Soflens. Over the following fifteen years, I led over 150 assignments involving both soft and gas permeable contact lenses, becoming, in that period, the “guru” of the contact lens industry.

But one of the most interesting assignments, in the fall of 1979, involved my traveling all over the United States and Europe to investigate possible technical partners for a Japanese company interested in entering the contact lens business.

In September of that year, after completing my U.S. visits, I traveled to Europe, visiting London, Paris, Strasbourg, Frieburg, Frankfort, back to London and finally, home to Boston to prepare a final report. (For some anecdotes from my first trip through Europe, see the following writeup - My First European Trip.) In November I traveled to Tokyo to present the results of my study. An Arthur D. Little (ADL) colleague and I flew to Tokyo via New York City on a Friday, arriving on Saturday. The following day, Sunday, I returned a phone call to another client who had left an urgent message that he desperately needed to speak with me and that I should call him at home over the weekend.

At 8 AM Tokyo time, which was about 7 PM (the previous day) in the U.S., I reached Steve Martin of Ciba Geigy (the other client) and he asked me the strangest question. He told me that I was the No. 1 contact lens expert in the U.S., and he wanted to know who was No. 2? Apparently, his Swiss parent company had heard my name from so many people that they wanted another name to get another view of the industry. I told him that there wasn’t anyone else doing what I did and he agreed. He had himself made many calls around the industry and had only gotten my name. He said that he was going to let the Swiss people know this and would call me the following Thursday and probably give me another assignment.

As it was, he called me back the following Wednesday while I was still in Tokyo (leaving the next day to return to the states), and told me that he needed me to travel to Germany the following Sunday to evaluate the technology of a German contact lens company (Titmus Eurocon) in which he was interested. (Since I was planning to recommend the same company to our Japanese client, I politely asked him not to buy them until, at least, I could deliver our final report to the Japanese client!)

So, I arrived home that Thursday, wrote and sent my proposal to Steve (Ciba Geigy) and met him at the Newark airport that Sunday prior to my overnight trip to Germany. I was part of a four or five men team (the others being optometrists and ophthalmologists) who were being sent to Germany to evaluate the German company’s technology.

We flew overnight, arrived in country early the next morning and immediately went to work at the German company. After spending the day in discussions, the company officials offered to take us out for dinner and entertainment. With all of my recent travels, I was literally out of it and politely declined and went to bed – I understand the rest of the group partied hard into the night – I have no idea how!

To make a long story short, after spending about three days in Germany, I came home, wrote my report and later heard that it was the influential piece of Steve’s presentation to management that gave him the go ahead to acquire the German company’s technology and to start CibaVision in 1980. He became its first president.

There are a couple of other stories about my role in advising companies that entered into the contact lens business. Here’s another that had an interesting twist.

Besides Ciba Geigy (CibaVision), I was also involved in the technical assessment of Frontier Contact Lens in Jacksonville, FL, for Johnson & Johnson, which they later acquired, and which became Vistakon.

In an earlier assignment for J&J, I did an assessment of Wesley Jessen in Chicago, but they passed on that company. However, about six months later, I was asked by Schering-Plough to visit in New Jersey about their potential acquisition of Wesley Jessen. I dutifully told them that yes, I had prepared a report on WJ, but I was under a confidentiality agreement not to discuss it. Schering said come on down anyway.

Lo, to my surprise, when I got to their offices, I was presented with a copy of my report and asked to discuss it! My guess is that the president of WJ (Orrin Stine) had given them a copy, given to him by the people at J&J. (I recently asked Orrin, but he doesn’t recall having a copy of my report.) Since I now felt that the confidentiality agreement was no longer valid, I did discuss my report and Schering did acquire WJ, which, as I recall, they later sold to Ciba.

So, I guess I did have quite an impact on the soft lens industry, both in the States and other parts of the world.

One last case and I’ll call it quits.

In August 1987, in a landmark case in the Tax Court in Wilmington, Delaware, ADL was hired by Baker & McKensy to assist in their representation of Bausch & Lomb in an international transfer pricing case against the IRS. It seems that B&L had transferred its technology to Ireland, where it was manufacturing most of its contact lenses then shipping them to the rest of Europe and to the U.S. for sale. This reduced substantially the amount of income B&L reported in the U.S. and allowed them to enjoy a much lower tax in Ireland. The questions before the Tax Court concerned the appropriate transfer price for the contact lenses and the royalty B&L Ireland owed to its U.S. parent company.

I was B&Ls contact lens industry expert and my ADL colleague, Dr. Irving Plotkin, their expert on foreign transfer pricing and royalties. (In fact he frequently worked both sides of the aisle, sometime being an IRS expert and other times working for the taxpayers!)

In any event, we prevailed and with a split decision by the tax court (mostly in B&L’s favor), saved B&L in the order of $15 million for the tax years in question, and perhaps tens of millions for succeeding years. This case set a precedent that became the law in international transfer pricing cases.

It was quite an experience being on the witness stand and being cross examined by the Government’s lawyers. In fact, I was so excited being in that position that I inadvertently answered one of the lawyer’s questions with a “Yes sir!”, when she was obviously a woman, who was very pregnant, and within weeks of delivering her baby!

Thursday, December 31, 2015

Stem Cells in Ophthalmology Update 24: Current Tables Now Online

My current stem cell/cell therapy tables are now online for anyone interested to access. Here is a brief description of what is available and how to access them:

Stem Cell/Cell Therapy Companies/Institutions Active in Ophthalmology

A list of forty-two companies and institutions working with stem cells/cell therapies for ophthalmic applications. The table lists collaborators, the cell type being used, and the applications for which the cells will be used.

A list of eighteen ophthalmic applications being studied and/or in clinical trials. The table includes the companies/institutions involved, the clinical trial status, and an active link for the clinical trial for those listed. (sixty-one active and completed clinical trials are shown.)

A list of the the eighteen ophthalmic applications and the sixty-one clinical trials showing the number of patients to be studied in each trial and the number studied to date (that I am aware of). Active links are provided for each ongoing or completed trial.

This article, published in the February 2015 issue of The Ophthalmologist, describes the use of stem cell-derived retinal progenitor cells (RPCs), that are being investigated for reviving/repairing/rejuvenating damaged photoreceptors to bring back sight to those who have lost it due to a retinal degenerative disease, including choroideremeia (CHM), retinitis pigmentosa (RP), Leber’s congenital amaurosis (LCA) and Stargardt’s disease (Stargardt Macular Dystrophy - SMD). It discusses the four companies that are conducting clinical research, as well as the work underway at several university and institutional laboratories.

With the likelihood of a gene therapy and/or a stem cell treatment for retinal diseases to be approved for marketing within the next two to three years, it is time for the ophthalmic community – the suppliers, practitioners, patients and payers – to start thinking about how much these regenerative medicine treatments are likely to cost, and how patients and the healthcare system will pay for them..

In The Economics of Gene Therapy, appearing in the May 2015 issue of The Ophthalmologist, I propose a pricing model for Regenerative Medicine in Ophthalmology, based on the population of patients to be treated, and suggest that an annuity program model, based on performance and duration of efficacy, could be used to pay for it.

An update of the latest clinical information in the use of gene therapy in treating several retinal diseases, including Leber’s Congenital Amaurosis (LCA); the wet form of Age-Related Macular Degeneration (wet-AMD); Choroideremia (CHM); Stargardt’s Macular Dystrophy (SMD); Retinitis Pigmentosa (RP); and Ushers Syndrome (US). Included is the proposed model of pricing for some gene therapy treatments, based on the population of patients likely to be treated.

Optogenetics is the introduction of protein-based, light-activated chemicals into still functional retinal cells in the vision chain, that upon activation, send electrical signals along the optic nerve to the brain, providing rudimentary vision, that was lost with the death or damage of the photoreceptors.

This report, The Optogenetics Option, describes the efforts of four companies and ten universities, using either gene therapy, or other means, to deliver light-activatable proteins or chemicals (photoswitches) to still functioning cells within the retina (ganglion and/or bipolar cells) or, in some cases, the use of light activatable implants, that will deliver light signals to the brain to provide some rudimentary vision when the photoreceptors, that normally provide that function, cannot.

Blog Articles Published in 2015

2015 was another busy year in writing about new developments in treating retinal diseases. During the year, I published seven blog entries (and another four published articles - to be indexed separately). Here are the highlights of the blog writeups:

Since I last wrote about Iluvien, Alimera Sciences and pSivida have announced additional marketing approvals for its use in treating chronic DME. The product is now approved for use in fourteen countries, including the U.S. In addition, pSivida is about to begin a Phase III study of its Medidur device for the treatment of uveitis, which should lead to a fast-track to approval.

But the real reason for this update was the recently published story about how an eye doctor reached out to Paul Ashton, CEO of pSivida, to package an old HIV anti-viral, ganciclovir, in his drug delivery system, to save the sight of a person undergoing chemotherapy for leukemia, who also needed a bone marrow transplant. The chemo and radiation treatment for the bone marrow transplant weakened his immune system, preventing control of his cytomegalovirus condition that began attacking his retina. Instead of painful weekly anti-viral injections, the doctor sought to use Paul’s drug delivery system to systemically treat the virus in the eye.

With the presentation of the three-year safety results of the INTREPID study (at EURETINA), to evaluate the safety and efficacy of the Oraya Iray Therapy in conjunction with as-needed anti-VEGF injections for wet AMD, and the recent collaboration agreement with Carl Zeiss Meditec, Oraya Therapeutics is well on its way in implementing its growth strategy in commercializing Oraya Therapy in Europe and, some day, in the U.S.

The company now has nine centers providing therapeutic treatment in Europe; four centers in the UK, one in Switzerland, and four in Germany.

To read more about this combination treatment to reduce the number of anti-VEGF treatments needed to control wet AMD, and the collaboration agreement with Carl Zeiss Meditec, please see: http://tinyurl.com/OrayaUpdate3

Avalanche Biotechnologies in Menlo Park and the University of Washington in Seattle announced a licensing agreement to develop the first gene therapy treatment for treating color blindness. The deal brings together a gene therapy technique developed by Avalanche with the expertise of vision researchers at the University of Washington.

In addition, Avalanche will incorporate research licensed from UCal Berkeley to deliver the gene therapy treatment non-surgically via an injection into the vitreous, rather than into the retina.

As Crystal Gayle sang in her smash hit, `Don't It Make My Brown Eyes Blue', now (soon) you will be able to permanently change your brown eyes to blue. A California company has come up with a laser procedure that will safely accomplish this in about 30 seconds per eye. Human clinical testing is underway and the company, Strōma Medical, hopes to have the procedure on the market (outside of the U.S. first) in less than two years, once the clinical trials are completed.

My article about the use of lasers to treat floaters, written five year ago, remains the most widely read piece on my blog. I frequently am asked if I have updated the list of doctors who now use lasers to treat floaters - in addition to the three I profiled in my U.S. writeup (Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis) and the six doctors in the UK/Europe piece (Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis in the UK and Europe).

I took notice when Ellex Medical announced a new YAG laser specifically for treating floaters in the fall of 2012, and about six months ago, I decided to request a list of doctors who have obtained the laser, and were now treating patients’ floaters. Better than a list, Ellex decided, to respond to my request, by building an app to locate doctors using their laser and put it on their website. That app is now active and is applicable to doctors worldwide using the new Ultra Q Reflex YAG laser to treat floaters. As of June 30th, there are 58 physicians listed worldwide using this laser.

Some insight into the Spark Therapeutics Phase III clinical trial results and longevity data. In this report, the company’s principal investigator, Dr. Stephen Russell presented highlights of the initial findings in this important Phase III clinical trial, that could lead to the first gene therapy approval in the United States.

Basically, it was found that the injection of SPK-RPR65 did lead to increased functional vision for the treated patients, compared to the control subjects - and the effect appears to last for over three years, based on the original patients treated in the Phase I study.

Three German ophthalmological groups provided guidance for German ophthalmologists to better identify those patients with wet AMD that might benefit from the use of the Iray Stereotactic Radiotherapy System as an adjuctive treatment to the use of anti-VEGFs in the treatment of neovascular macular degeneration, based on studies conducted by the company to date.

Tuesday, October 20, 2015

When I last updated the progress of Oraya Therapeutics, in January of this year (Oraya IRay Update 3: Oraya Now Operating at Nine European Centers and Partnership with Carl Zeiss Meditec), I noted the collaboration agreement between Oraya and Carl Zeiss Meditec to provide funding to Oraya over a period of up to two years for the implementation of Oraya's growth strategy, and I reported on the three-year INTREPID safety results, presented the previous September. Here now is the latest information on the progress of the company to bring this adjunctive treatment for the wet form of AMD to the professions.

The German Ophthalmological Society, the Retina Society and the Professional Association of German Ophthalmologists (DOG) have issued a joint opinion on the adjunctive use of radiotherapy with Oraya Therapeutics' IRay Stereotactic Radiotherapy System for wet AMD. Their opinion makes it possible for ophthalmologists throughout Germany to identify patients that can benefit from Oraya Therapy in conjunction with anti-VEGF treatment.

Oraya Therapy is currently commercially available at eleven sites in Europe, with more than 550 patients treated to date with Oraya Therapy in three European countries - Germany, Switzerland and the United Kingdom.

According to the opinion, which takes the study data published to date into account, adjunctive stereotactic radiotherapy of neovascular AMD with the IRay system can be considered on an individual basis. Some of the parameters that ophthalmologists should consider include:

● If symptoms of choroidal neovascularization (CNV) activity such as intra-retinal fluid of bleeding are present, corresponding to a recommendation of VEGF inhibitors;

● If the ongoing anti-VEGF therapy has taken place over a period of at least six months, thus ruling out undertreatment; and,

● If despite intensive injection therapy, no change in the activity state of the CNV is achieved and there is no reasonable expectation of a decrease of the required high frequency of retreatment for the future.

"The joint opinion now provides guidance for ophthalmologists throughout Germany to identify those patients who can benefit from Oraya Therapy for wet AMD. There is a large patient population that does not respond well to anti-VEGF monotherapy, and our aim is to offer these patients in Germany an additional option to maintain their vision and also decrease the burden of frequent injections," said Oraya Therapeutics CEO Jim Taylor. "We are well positioned with our IRay system at major university eye clinics in Germany, and will continue to expand our presence to make the therapy available to the patients who qualify and elect to pursue this alternative."

Wednesday, October 14, 2015

My article updating the latest information on the status of gene therapy clinical trials, What’s New in Gene Therapy for Ophthalmology? was published in the October issue of Retinal Physician. The final draft was submitted just prior to this important news from Spark Therapeutics providing information about their Phase III clinical trial results.

Principal Investigator Stephen R. Russell, MD, of the Stephen A. Wynn Institute for Vision Research at the University of Iowa, presented Phase III data highlighting the rate, breadth and magnitude of changes following administration of SPK-RPE65 to patients with Leber’s Congenital Amaurosis (LCA), at the Retina Society Meeting held in Paris on October 10th.

In addition, Dr. Russell presented data on the three-year durability of improvements in the same measures of functional vision and light sensitivity in a cohort of subjects from the earlier Phase I trial.

This presentation built on top-line results of a randomized controlled multi-center Phase III trial previously announced by Spark on October 5, which demonstrated a highly statistically significant improvement in the intervention group compared to the control group in the primary endpoint and two of three secondary endpoints.

Data presented highlighted a mean improvement in the functional vision of intervention subjects (n=20) of 1.9 specified lux levels, compared with an improvement of 0.2 specified lux levels in control subjects (n=9) as measured by the change in bilateral mobility testing (MT) between baseline and one year in the modified intent-to-treat (mITT) population. The mITT population (n=29) includes all subjects that received SPK-RPR65, and only those who continued beyond the baseline study visit. Two subjects in the intent-to-treat (ITT) population (n=31) that were randomized but never received SPK-RPE65 are excluded from this efficacy analysis population. Thirteen of the 20 subjects receiving SPK-RPE65 were able to pass the MT at one lux at year one, demonstrating maximum improvement measurable on the MT score. None of the nine control subjects followed was able to pass MT at one lux at year one.

(*FST is a full-field light sensitivity threshold test. As RPE65-mediated retinal dystrophies primarily affect rod photoreceptors first, night blindness and loss of peripheral vision are typically the presenting symptoms; central vision may be relatively spared initially. Thus FST was the first hierarchically-arranged secondary as opposed, for example, to visual acuity. It is more reflective of the underlying pathophysiology of the disease.)

Dr. Russell presented additional top-line analyses from the pivotal Phase III trial showing the rapid and sustained impact of SPK-RPE65 throughout the entire one-year study period. Significant differences emerged in both MT and FST by the first study visit, at 30 days. These effects were reproduced consistently at each subsequent study visit (at days 90, 180 and one year).

Dr. Russell said, "It's exciting to see a consistency of improvement between the functional vision and visual function. The parallel effect seen in the prompt response in both the primary and first secondary endpoints highlights a critically important finding from the trial: that functional improvements measured through the mobility test change score correspond closely with the physiologic impact seen through FST."

Figure 1: Phase III Trial of SPK-RPE65: MT and FST Over Time (mITT)

In addition, Dr. Russell presented data on the durability of effect after three years as measured by MT and FST in a cohort of subjects that participated in the Phase 1 open-label study, and would likely have met the eligibility criteria for the Phase 3 trial. All of these subjects continue to experience a durable improvement over three years from the time of administration to the contralateral, or second eye, with observation ongoing. These subjects received the same dose and volume of SPK-RPE65 that was used in the pivotal Phase 3 trial. The figures below reflect data from all subjects available for follow-up at each time point reported. Spark and the clinical investigators continue to follow study participants to evaluate the durability of response, and will provide further updates in the future through a series of peer-reviewed presentations and publications.

"We are pleased to provide these additional informative data, the totality of which highlight the rapid, sustained and durable effect associated with SPK-RPE65 across multiple functional and physiological parameters, at time points ranging from 30 days to three years," said Jeffrey D. Marrazzo, co-founder and chief executive officer of Spark. "We will continue to analyze the data from our groundbreaking pivotal Phase 3 trial in order to further elucidate the potential positive, meaningful impact that SPK-RPE65 can have on the lives of patients with RPE65-mediated blinding conditions."

Figure 2: Phase 1 Trial of SPK-RPE65: Durability of MT and FST Over Time

Pivotal, Phase 3 Trial Overview

The pivotal Phase 3 trial of SPK-RPE65 is the first successful randomized, controlled Phase 3 trial ever completed in gene therapy for a genetic disease. The multicenter trial randomized 31 subjects with confirmed RPE65 (LCA) gene mutations. The ITT population included 21 subjects in the intervention group and 10 in the control group.

For the primary endpoint, subjects were evaluated at multiple time points over the course of one year for their performance in navigating a mobility course under a variety of specified light levels ranging from one lux (equivalent to a moonless summer night) to 400 lux (a brightly lit office) using the bilateral testing condition. Each attempt was recorded, and the videos were sent to independent, centralized, masked graders to assign a pass/fail score based on speed and accuracy with which the subjects navigated the course.

In addition to the primary endpoint, the statistical analysis plan included three secondary endpoints tested statistically in the following hierarchical order:

● Change in MT score for the assigned first eye, which compares the MT performance between baseline and year one for the first eye injected for the intervention group and, for the control group during the control year, the first eye injected after they crossed over.

● Visual acuity (VA) testing, which measures changes in central vision by assessing the ability of the subject to read a standard eye chart.

A summary of top-line efficacy results follows:

Primary outcome (ITT)

MT change score, bilateral p = 0.001

Secondary outcomes (ITT)

FST, averaged over both eyes p < 0.001

MT change score, first injected eye p = 0.001

VA, averaged over both eyes p = 0.17

So What Does All This Mean?

In a story about the trial results published by Bloomberg Business News, the reporters commented, “A gene therapy maker showed this week it could make blind children and adults see. But the big question left is how long the effect will last.”

“Much depends on the answer, including how much the company can charge for the drug -- a price tag some say could be more than $1 million a patient.”

The company has shown the effect has lasted for as long as three years without degradation of vision in some patients, providing back functional vision to those nearly blind children treated in the initial clinical trial.

According to Dr. Russell, the principal investigator, "Investors will look at the data and are going to go, `Wow this is the best data we've seen, not just in the eye, but on gene therapy, period' and they're right,"

Yet he cautioned that more information is needed before the drug can be considered a cure. While it produces a missing enzyme needed to sense light, it can't restore light-sensing cells that have already died off due to this progressive disease. In the initial study results, released on October 5th, one standard measure of vision, visual acuity, didn't improve by a statistically significant amount. (But, functional vision did!)

Spark also hasn't finalized and published data on individual patients, and it's possible that some responded better than others. “Age in particular may be a factor in how much a patient can improve,” said Dr. Russell. The company said in its statement that no serious adverse events have been seen so far in the trial.

So, the question remains, is this the “forever fix”, as author Riki Lewis has written in her book on gene therapy, or something less? Time will tell. But this is certainly an important step forward for the treatment of an inherited retinal disease.

Tuesday, September 01, 2015

Gene Therapy in Ophthalmology Update 16: Current Tables Now Online

My current gene therapy tables are now online for anyone interested to access. Here is a brief description of what is available and how to access them:

Gene Therapy

Gene Therapy Companies/Institutions Active in Ophthalmology

The table lists more than forty-two companies and institutions actively pursuing gene therapy solutions to ophthalmic diseases. The table shows the delivery viral platform, the gene type being used (where known), the application, and clinical status.

This table lists the twenty-two ophthalmic indications, the company/institutions involved, the clinical status, and the clinical trial number. (Thirty active clinical trials are listed, with live links.)

Tuesday, June 30, 2015

Using Lasers to Treat Vitreous Floaters: An Update

Since my first article on the use of a YAG laser to treat floaters (Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis) appeared in this space in August 2010, it has become the most popular/read write-up that I have posted. About 10% of all visitors to my blog come to read that article - and I’ve had over 215,000 unique visitors. One of the most frequent questions I get asked is, is there anyone close to where I live that does the procedure? Since I haven’t kept track of who besides the three doctors I featured in that first write-up are now doing the procedure, and since Ellex Medical (Ellex) now produces and markets a specialized laser (the Ultra Q Reflex) specifically to treat floaters, I decided it was time for this update.

While there are several YAG lasers on the market, none until now were designed specifically for the treatment of floaters.

"The Ultra Q Reflex is optimized for performing YAG laser treatments both in the anterior segment and posterior segment - making it ideal for the all conventional YAG laser treatments such as capsulotomy and iridotomy, as well as YAG laser vitreolysis for the treatment of floaters," added Mr. Spurling.

Ultra Q Reflex for Nd:YAG Laser Vitreolysis

Floaters (vitreous strands) are small bundles of collagen fibers located in the eye's vitreous, which cast visual shadows that impede quality of vision. Often considered benign, they are a result of degenerative vitreous syndrome (DVS; the natural breakdown and clumping of collagen in the vitreous) and posterior vitreous detachment (PVD; the age-related separation of the vitreous from the retina).

To date, surgical removal of the vitreous (vitrectomy) has been the standard approach to the treatment of floaters. Highly invasive, the procedure carries a significant risk of complications, such as infection, retinal detachment, macular edema, anterior vitreous detachment and residual floaters.

The proprietary slit lamp illumination tower design of the Ultra Q Reflex converges the operator's vision, the target illumination, and the treatment beam onto the same optical path, and focuses them onto the same optical plane as the treatment beam. This minimizes the potential for focusing errors and the risk of damage to the natural lens or the retina -- making the Ultra Q Reflex ideal for the treatment of floaters. In contrast, conventional YAG lasers offer a limited view of the vitreous, which can make it difficult to visualize vitreous strands and opacities.

I contacted Ellex Laser management and requested a list of the U.S. doctors who have purchased this laser and who now use it to treat their patient’s vitreous strands/floaters. The company, in response to my request, has set up an application on its website, called “Find a Physician”.

By entering your location, a map will appear which will locate doctors near you that have access to this specialized laser and use it to treat vitreous floaters by performing laser vitreolysis. The link to the app is: http://www.floater-vitreolysis.com/find-a-physician/

PS: The app works worldwide!

(As of June 30th, there are 58 physicians across North America, Australia, Asia, and parts of Europe who have decided to be referenced in the physician finder.)

Wednesday, April 08, 2015

A Laser Process for Changing Brown Eyes Blue

`Don't It Make My Brown Eyes Blue' was a smash hit song(1) for Crystal Gale in 1977. But it has been a wish for many a young girl with brown eyes (and even some older ones and perhaps some men) ever since. Over the years it has been possible to turn your brown eyes blue using contact lenses, first lightly tinted ones, which really didn’t do much for dark brown eyes, and later opaque tinted lenses, which would cover brown pigmented eyes and really turn them blue (or green or even other colors), although they created an opaque light eye, which does not exist in nature and thus looks contrived. There are even a couple of surgical procedures that can transform the iris, or enhance/darken the edge, but the question of safety quickly arises with any surgical procedure.

So, a week ago, when my wife told me what she had just seen that there was a laser process to turn brown eyes blue, on The View, I replied, “No way”. You see, I was a consultant to the medical laser industry, involved in the use of lasers in both ophthalmology and cosmetic surgery, for over twenty years and had never heard of lasers used in this way. Just to be sure, I Googled it, and much to my surprise, yes, a company, Strōma Medical Corporation, in Laguna Beach California, is developing a permanent, non-surgical laser procedure that will turn brown eyes blue!

I found an article written for Ophthalmology Business(2) that explained how they were doing it. It also listed a couple of well-known ophthalmologists – Perry Binder and Marguerite McDonald, who I know on a personal basis – that are involved with the company, on their Medical Advisory Board, thus assuring me that this business was legitimate. I got in touch with my ophthalmologist friends and they put me in touch with the Chairman and Chief Scientific Officer of the company, Dr. Gregg Homer, to learn more.

What I have learned is that the company has developed a unique, low intensity, highly specialized laser and diagnostic aiming system (with computerized iris mapping and tracking), that targets the brown pigment on the front surface of the iris, removing some or all of that pigment, thereby revealing the natural blue eye lying below. (The blue in an eye is actually the result of the scattering of white light entering the iris, by tiny grey collagen fibers called “stroma”, and the reflection of the shorter blue light, similar to the light scattering of sunlight by atmospheric molecules that makes the sky appear to be blue.)

A half treated eye (for illustration purposes).

As explained by Dr. McDonald in the Ophthalmology Business article, describing how the procedure works, “This is a Q-switched neodynmium YAG laser, which produces a very highly discriminatory photo-absorbed frequency. The laser fires a series of small, computer-guided pulses across the iris, to photo-disrupt the stromal melanocytes (the brown pigment). Because of the photo-absorption properties of this laser, the energy passes through the clear cornea and it very selectively hits the brown melanocytes, leaving the cornea and the posterior iris stroma totally undisturbed. The photo-disrupted melanocytes release cytokine protein molecules into the anterior chamber and the cytokine signal recruits macrophages...that engulf and digest the photo-disturbed melanocytes as cellular debris.”

To put it in simpler terms, the laser beam “breaks up” the brown pigment in the front part of the iris into much smaller particles, similar to the way lasers are used to remove tattoos, by a process known as “selective photothermolysis”(3). This phenomenon, invented by Drs. John Parrish and Rox Anderson of the Wellman Laboratories of Photomedicine at Massachusetts General Hospital, uses the principle of delivering pulsed laser energy to a selected chromaphore within the target tissue, without damaging surrounding tissue.

Illustration of the iris in cross section, showing the anterior border layer, which is the target of the Strōma Medical process.

The smaller particles are then digested by the macrophages formed and eliminated from the iris and from the anterior chamber via the normal liquid outflow channels in the eye.

The Story Behind the Story

According to Dr. Homer, he became interested in the concept of changing eye color in the late 1990s, discovering a paper in the literature on iris pigmentation by RC Eagle Jr.(4) “I finally found that paper, which wasn’t available digitally, and I thought, ‘Now that we’ve done so much work with lasers on dermal pigment, it should be fairly easy to remove that iris pigment safely, which should, in turn, reveal a blue eye.” He went on, “Around 2001, I personally funded a small study at Cedars-Sinai Eye Institute in Los Angeles. We took brown-eyed rabbits and proved the concept, showing that we could change an eye’s color. These rabbits don’t’ have blue eyes, but what we showed is we could (safely) remove the pigment.”

In 2009, Dr. Homer and his colleagues raised $2 million in a Series A round to form the company, build a prototype laser device, and open a clinical trial. They achieved their goals, successfully treating 17 patients in Mexico with solid efficacy and no adverse events.

The Procedure

The Strōma Medical procedure is non-invasive. It involves no incisions or injections of any kind. In fact, other than the use of a small device to help keep the patient's eyelid open during the procedure and the application of a mild topical medication, there is little or no contact with the patient's eye.

The patient sits in front of the Strōma laser, and his or her head is stabilized. The patient is instructed to direct the untreated eye toward a tiny animation, located about one foot from the patient's eye, while the procedure is completed. The procedure is then repeated to treat the other eye.

The Strōma Medical Laser work station.

The treating physician will inform the patient when he or she may drive and return to work. In most cases, the patient should be able to do so shortly after the procedure. For the first week or so following the procedure, the irises will get darker. Thereafter, they will grow progressively lighter, revealing the underlying natural blue color. The full color change process should take two to four weeks following the procedure.

Where Does the Process Stand?

According to Dr. Homer, the Strōma Medical laser process, which takes about 30 seconds per eye, is still being clinically tested before being released commercially, first outside of the U.S.

To date, the company has completed preclinical studies on 50 Dutch-belted rabbits, and clinical studies on 17 human subjects treated in Mexico. The company is preparing its’ first large-scale pilot clinical study in Costa Rica, involving about 20 patients. Following the successful completion of that pilot study, the company plans to treat about 100 additional patients in multiple countries and follow them for a predetermined length of time.

The company plans to release the product when it and the governing regulatory bodies are satisfied with the safety and efficacy of the procedure. Due to the relative cost and complexity of releasing a cosmetic medical device in the United States, they expect to release the procedure outside the United States first. The order of release in the non-U.S. territories will depend upon the market demand and regulatory environment in each territory.

Remaining Questions

The technique appears to be non-invasive, safe, and painless. The laser treats only the front of the iris and does not enter the pupil or treat any portion of the inside of the eye where the nerves affecting vision are located.

But several questions do remain:

1.What happens to the pigment debris that leaves the iris? Will that debris clog up the normal drainage channels in the front of the eye, which can in turn cause glaucoma?

Strōma Medical claims that the digested particles released by the process are too fine to cause glaucoma and can easily pass through the trabecular meshwork and out into the anterior chamber -- and that even if there were any complications, they would be short-term and easily remedied, including the use of a standard laser procedure - selective laser trabeculoplasty (SLT), commonly used to eliminate pigment from the trabecular meshwork that might contribute to a rise in intraocular pressure. However, a small risk still remains, and the remaining studies are intended to address that risk prior to commercial release.

2. Don’t the pigmentary layers of the iris provide ultra-violet and infrared light protection to the lens and the retina in the back of the eye? Won’t removal of one of the layers increase the likelihood of cataracts and increased retinal problems due to increased ultra-violet and infrared light exposure?

Dr. Homer acknowledges that naturally light eyes tend to be more sensitive to bright light. He explains, however, that light eyes are not only less pigmented on the front surface of the iris, but throughout the eye, including the retinal nerves in the back of the eye that respond to light. Light sensitivity, he maintains, is the result of less retinal pigment, not less pigment on the front surface of the iris. Because the procedure is limited to the removal of pigment from the front surface of the iris, its removal would not increase light sensitivity. Instead, the procedure is able to achieve something that nature does not – a light eye without light sensitivity.

3. How much will the procedure cost?

According to Dr. Homer, the procedure would likely cost about $5,000 for both eyes in the U.S., but the physicians doing the procedure would set the price, not the company itself, and it would likely vary depending upon territorial demand curves and currency fluctuations.

4. What will be the costs to the ophthalmologists?

The financial model for the procedure will follow LASIK – the laser device (which will be sold or leased), a maintenance contract for the device, and a per-procedure fee. The pricing has not yet been determined, but the company expects the device and service contract to cost less than those for LASIK, and the per-procedure fee to cost more.

5. Have you estimated the size of the market? Perhaps using the tinted contact lens market as an example?

According to market research done by the company, the relevant potential worldwide market for manufacturers of eye color changing products will be those people who have dark eyes (brown or hazel), are affluent enough to afford the procedure cost, and are 20-60 years of age. When the market is mature, 10.2 million people worldwide could have their eye color changed each year. The largest patient population for the Strōma Medical’s system may be in India and China, followed by Central and South America, Southern Europe, Japan, Korea, the Middle East, and the United States.

Further, the company believes that the market for permanent eye color change will be the fastest growing segment of the aesthetics market over the next ten years. The market will be made up of individuals who have the money and the desire to change their eye color. The annual sustainable, and achievable market opportunity for companies in this space is estimated to approach $2.9 billion in five years. For physicians and their clinics, the market opportunity could be $9.3 billion. Early adapters of the technology will come from the 25 million patients who currently wear colored contact lenses, and the estimated 70 million patients who have stopped wearing them for aesthetic, comfort or an adverse response reason. But, the market could be much larger as the consistency of the results and a positive safety profile is confirmed through solid clinical studies.

6. Finally, do you have any IP protection? What’s to prevent a laser manufacturer to build both a laser and a diagnostic and aiming system to compete directly with you - in fact, isn’t there an entity in Barcelona that is now providing the service?

The company has an extensive international patent portfolio, which includes international patents covering several critical elements of the laser device and patents in the U.S., Singapore, and Australia covering any method or system using any form of electromagnetic radiation to alter iris color. The company also has additional protection covering various ancillary features of the procedure, such as its proprietary iris mapping and tracking technology, scan pattern, and beam profile.

The company claims that the physician in Barcelona was using an off-the-shelf laser designed for laser iridotomy and posterior capsulotomy, which is ill-suited for iris color change. As a result, many patients were injured – the local medical societies opened an investigation, and the physician appears to have discontinued the procedure.

To obtain more information about the process and the Strōma Medical laser, please visit the company’s website at this link.

About Me

Until my retirement in 2005, I was a consultant to the ophthalmic industry for over 30 years, and to the medical laser industry for over 20 years.
I was with Arthur D. Little for 25 years and ran my own consulting company, Spectrum Consulting for 11 years, including publishing the monthly newsletter, Executive Laser Briefing.